Increase in antibody titers from H5N1 vaccine confers cross-protection against highly pathogenic H5N1 influenza virus

H5N1 is a highly pathogenic avian influenza (HPAI) virus that has exhibited a significant capacity for adaptation and transmission among diverse mammalian species, thereby raising concerns regarding its pandemic potential. Vaccination constitutes a crucial strategy for controlling the spread of HPAI, rendering the development of effective vaccines and treatments for H5N1 a paramount public health priority. In 2005, Sinovac Biotech Ltd., China, developed an inactivated H5N1 vaccine with an aluminum hydroxide adjuvant, employing the A/Vietnam/1194/2004 (clade 1) strain for potential influenza pandemics or emergencies. However, the neutralizing efficacy of this vaccine against currently circulating H5N1 strains, especially those of clade 2.3.4.4b, remains uncertain. In the present study, a pseudovirus platform and clinical human immune sera from H5N1 vaccine recipients were utilized to assess the neutralizing antibody responses to globally circulating H5N1 strains, focusing on the antigenic match between the vaccine strain and circulating strains. The results indicate that sera from participants who received two doses of the H5N1 vaccine with aluminum hydroxide adjuvant manifested broad-spectrum protective effects against H5N1 strains only when high antibody titers were attained. By analyzing the correlation between pseudovirus-based neutralizing assay (PBNA) titers and seroconversion rates (SCR) against H5N1 strains, it was estimated that a PBNA titer of at least 1:980 is required to achieve a cross-protection rate above 60%. The findings suggest that with increased antibody titers, China’s H5N1 vaccine is capable of generatingcross neutralizing antibodies against H5N1 strains. Until new H5N1 vaccines are developed, measures such as using a more efficacious adjuvant, increasing the number of doses, or adjusting the dosage could enhance antibody titers, enabling this vaccine to function as a bridging measure to prevent further outbreaks of HPAI.